More than 28,000 medical professionals received warning letters from HMRC, and tax experts say investigations into practices could go on for years without GPs' knowledge.
Just 1,500 medical professionals came forward to declare underpaid tax as part of this summer's amnesty.
Paul Malin, director of tax investigations at consultants BTG Tax, said HMRC could spend years dealing with all the cases because of a shortage of tax inspectors. Even those who have come forward may still be investigated if they have different irregularities they have not disclosed, said Mr Malin.
He warned that HMRC was likely to prosecute a number of doctors as part of an aggressive new approach to tax-avoidance.
'It has a selective prosecution policy; in essence what it does is to pluck out a high-profile case and prosecute as a deterrent to others,' he said. 'It could be a low number but I do expect some to happen.'
One doctor was found to have owed a million pounds in unpaid tax, said Mr Malin.
He warned that HMRC had recently doubled its maximum fines and was preparing to 'name and shame' those who had underpaid tax.
The amnesty ended in June but HMRC is still advising GPs who think they may have underpaid tax to declare it as soon as possible.